Scientists at the University of Nottingham, UK, have discovered a previously undetected layer in the cornea. The breakthrough, announced in a study published in Ophthalmology, could help surgeons to dramatically improve outcomes for patients undergoing corneal grafts and transplants.

The new layer has been dubbed the Dua’s Layer after the academic Professor Harminder Dua who discovered it.

Professor Dua, a professor of ophthalmology and visual sciences, said: “This is a major discovery that will mean that ophthalmology textbooks will literally need to be re-written. Having identified this new and distinct layer deep in the tissue of the cornea, we can now exploit its presence to make operations much safer and simpler for patients.

“From a clinical perspective, there are many diseases that affect the back of the cornea which clinicians across the world are already beginning to relate to the presence, absence or tear in this layer.”

The newly discovered layer is between the corneal stroma and Descemet’s membrane. Although it is just 15 µm thick, it is incredibly tough and is strong enough to be able to withstand one and a half to two bars of pressure.

The scientists proved the existence of the layer by simulating human corneal transplants and grafts on eyes donated for research purposes to eye banks located in Bristol and Manchester.

During this surgery, tiny bubbles of air were injected into the cornea to gently separate the different layers. The scientists then subjected the separated layers to electron microscopy, allowing them to study them at many thousand times their actual size.

Understanding the properties and location of the new Dua’s layer could help surgeons to better identify where in the cornea these bubbles are occurring and take appropriate measures during the operation. If they are able to inject a bubble next to the Dua’s layer, its strength means that it is less prone to tearing, meaning a better outcome for the patient.

The discovery will have an impact on advancing understanding of a number of diseases of the cornea, including acute hydrops, Descematocele and pre-Descemet’s dystrophies.

The scientists now believe that corneal hydrops, a bulging of the cornea caused by fluid build up that occurs in patients with keratoconus, is caused by a tear in the Dua layer, through which water from inside the eye rushes in and causes waterlogging.

Better Gene Delivery from Cal Scientists
Researchers at the University of California, Berkeley, have developed an easier and more effective method for inserting genes into eye cells that could greatly expand gene therapy to help restore sight to patients with blinding diseases ranging from inherited defects like retinitis pigmentosa to degenerative illnesses of old age, such as macular degeneration.

Unlike current treatments, the new procedure—which takes as little as 15 minutes—is surgically non-invasive, and it delivers normal genes to difficult-to-reach cells throughout the entire retina.

Over the last six years, several groups have successfully treated people with a rare inherited eye disease by injecting a virus with a normal gene directly into the retina of an eye with a defective gene. Despite the invasive process, the virus with the normal gene was not capable of reaching all the retinal cells that need fixing.

“Sticking a needle through the retina and injecting the engineered virus behind the retina is a risky surgical procedure,” said David Schaffer, PhD, professor of chemical and biomolecular engineering and director of the Berkeley Stem Cell Center at the University of California, Berkeley. “But doctors have no choice because none of the gene-delivery viruses can travel all the way through the back of the eye to reach the photoreceptors—the light sensitive cells that need the therapeutic gene.

“Building upon 14 years of research, we have now created a virus that you just inject into the liquid vitreous humor inside the eye and it delivers genes to a very difficult-to-reach population of delicate cells in a way that is surgically non-invasive and safe. It’s a 15-minute procedure, and you can likely go home that day.”

The engineered virus works far better than current therapies in rodent models of two human degenerative eye diseases, and can penetrate photoreceptor cells in the eyes of monkeys, which are like those of humans.

Dr. Schaffer and his team are now collaborating with physicians to identify the patients most likely to benefit from this gene-delivery technique and, after some preclinical development, hope soon to head into clinical trials, he said.

The study was published on June 12 in the journal Science Translational Medicine.

Three groups of researchers have successfully restored some sight to more than a dozen people with Leber’s congenital amaurosis, which leads to complete loss of vision in early adulthood. They achieved this by inserting a corrective gene into adeno-associated viruses (AAV), a common but benign respiratory virus, and injecting the viruses directly into the retina. The photoreceptor cells take up the virus and incorporate the functional gene into their chromosomes to make a critical protein that the defective gene could not, rescuing the photoreceptors and restoring sight.

Unfortunately, the technique cannot be applied to most blinding diseases because the needle often causes retinal detachment, making the situation worse. Yet the standard AAV used in eye and other types of gene therapy can’t penetrate into tissue to reach the photoreceptors and other cells, such as retinal pigment epithelium, that need to be fixed. The retina is about 100,000 times thicker than an AAV, which is about 20 nanometers across.

Years ago, Dr. Schaffer set out to find a way to “evolve” AAV to penetrate tissues, including eye and liver, as a way to deliver genes to specific cells. To date he has generated 100 million variants of AAV—each carrying slightly different proteins on its coat—from which he and his colleagues selected five that were effective in penetrating the retina. They then used the best of these (7m8) to transport genes to cure two types of hereditary blindness for which there are mouse models: X-linked retinoschisis, which strikes only boys and makes their retinas look like Swiss cheese; and Leber’s congenital amaurosis. In each case, when injected into the vitreous humor, the AAV delivered the corrective gene to all areas of the retina and restored retinal cells nearly to normal.

When injected into the eye of a normal monkey, the virus penetrated cells spottily across the retina but almost completely in the fovea. Current viruses do not penetrate foveal cells at all.

Dr. Schaffer predicts that the virus can be used not only to insert genes that restore function to non-working genes, but can knock out genes or halt processes that are actively killing retina cells, which may be the case in age-related macular degeneration.


Study Tabs Cost Of Inefficient Drug Use at $200 Billion
Avoidable costs of more than $200 billion are incurred each year in the U.S. health-care system as a result of medicines not being used responsibly by patients and health-care professionals, according to a new study by the IMS Institute for Healthcare Informatics. This represents 8 percent of the country’s total annual health-care expenditures and amounts to millions of avoidable hospital admissions, outpatient treatments, pharmaceutical prescriptions and emergency room visits for patients.

The report— Avoidable Costs in U.S. Healthcare: The $200 Billion Opportunity from Using Medicines More Responsibly—examines six areas that contribute to unnecessary costs: medication nonadherence, delayed evidence-based treatment practice, misuse of antibiotics, medication errors, suboptimal use of generics and mismanaged polypharmacy in older adults. Together, these areas lead to unnecessary utilization of health-care resources involving an estimated 10 million hospital admissions, 78 million outpatient treatments, 246 million prescriptions and four million emergency room visits annually. The study found significant opportunities for improvement—to ensure that patients receive the right medicines at the right time, and take them in the right way.

“As our study makes clear, drugs are often not used optimally, resulting in significant unnecessary health system spending and patient burdens,” said Murray Aitken, executive director, IMS Institute for Healthcare Informatics. “Those avoidable costs could pay for the health care of more than 24 million currently uninsured U.S. citizens.”

The report finds that progress is being made to address some of the challenges that drive wasteful spending in many parts of the U.S. health-care system. Medication adherence among large populations of patients with hypertension, hyperlipidemia and diabetes has improved 3 to 4 percent since 2009. In addition, the proportion of patients diagnosed with a cold or the flu who inappropriately received antibiotic prescriptions has fallen from 20 percent to 6 percent since 2007. And, patients are now receiving lower-cost generic alternatives to branded medications, when available, 95 percent of the time.

The report’s key findings include:

•    Medication nonadherence drives the largest avoidable cost. Patients not adhering to their doctors’ medication guidance experienced complications that led to an estimated $105 billion in annual avoidable health-care costs. While the underlying reasons for nonadherence are varied and longstanding, the growing use of analytics and collaboration among providers, pharmacists and patients appear to be advancing both the understanding and effectiveness of intervention programs.

•    Delays in applying evidence-based treatment to patients lead to $40 billion in annual avoidable costs. The study analyzed four disease areas where patients either are not diagnosed early or treatment is not initiated promptly. The largest avoidable impact is seen in diabetes, where such delays increased outpatient visits and hospitalizations. A reduction in this source of avoidable costs is possible if insurance coverage is expanded, and at-risk patients are able to receive appropriate screening and diagnostic testing.

•    Some signs of improvement are evident in the responsible use of antibiotics. The misuse of antibiotics contributes to antimicrobial resistance and an estimated $34 billion each year in avoidable inpatient care costs. An additional $1 billion is spent on about 31 million inappropriate antibiotic prescriptions that are dispensed each year, typically for viral infections. There are encouraging signs that efforts to drive responsible antibiotics use are paying off, particularly in the declining number of prescriptions for the common cold and flu–viral infections that do not respond to antibiotics.

•    Efforts are under way to address the underlying causes of avoidable spending and to improve medication use, with initiatives advancing across the health-care landscape, including novel interventions, critical assessments of established solutions and pioneering models of stakeholder cooperation. Many of these initiatives involve a greater role for pharmacists, an integrated approach to addressing patient issues, alignment of financial incentives, and greater use of health-care informatics to guide decision-making and monitor progress.  REVIEW